ArticlePloS one2014
Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02502071 (Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 DiabetesL a Open-label Trial), which is not on this map. Cited by 67 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 DiabetesL a Open-label Trial
Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Uric acid in CKD: has the jury come to the verdict?Journal of nephrology · 2020Pooled it
- Effect of Bempedoic Acid on Serum Uric Acid and Related Outcomes: A Systematic Review and Meta-analysis of the available Phase 2 and Phase 3 Clinical Studies.Drug safety · 2020Pooled it
- Hyperuricemia increases the risk of acute kidney injury: a systematic review and meta-analysis.BMC nephrology · 2017Pooled it
- Effect of dotinurad versus febuxostat on the one-year eGFR slope in CKD patients with hyperuricemia: a retrospective cohort study.BMC nephrology · 2026Article
- Programmed cell death in gouty nephropathy: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Ferroptosis regulation by SGLT2 inhibitors: mechanisms and clinical benefits in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Increased serum uric acid-to-urinary urate excretion ratio with the kidney function decline in male CKD patients without diabetes: a retrospective cohort study.BMC nephrology · 2025Article
- Is uric acid a true antioxidant? Identification of uric acid oxidation products and their biological effects.Redox report : communications in free radical research · 2025Review
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- Article
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- Mitochondrial Oxidative Stress and Vascular Remodeling in Uric Acid Nephropathy: Mechanistic Insights and Therapeutic Implications.International journal of nephrology and renovascular disease · 2025Review
- The interplay between diabetes and atherosclerosis: A review of pathophysiological mechanisms.ARYA atherosclerosis · 2025Review
- Galangin Triggers Eryptosis and Hemolysis Through CaInternational journal of molecular sciences · 2024Article
- Coexposure to microplastic and Bisphenol A exhacerbates damage to human kidney proximal tubular cells.Heliyon · 2024Article
- Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Association between urinary uric acid excretion and kidney outcome in patients with CKD.Scientific reports · 2024Article
- Novel Insights into the Molecular Mechanisms of Atherosclerosis.International journal of molecular sciences · 2023Review
- Phosphatidylserine decarboxylase downregulation in uric acid‑induced hepatic mitochondrial dysfunction and apoptosis.MedComm · 2023Article
- Non-Haemodynamic Mechanisms Underlying Hypertension-Associated Damage in Target Kidney Components.International journal of molecular sciences · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mild hyperuricemia has been linked to the development and progression of tubulointerstitial renal damage. However the mechanisms by which uric acid may cause these effects are poorly explored. We investigated the effect of uric acid on apoptosis and the underlying mechanisms in a human proximal tubule cell line (HK-2). Increased uric acid concentration decreased tubule cell viability and increased apoptotic cells in a dose dependent manner (up to a 7-fold increase, p<0.0001). Uric acid up-regulated Bax (+60% with respect to Ctrl; p<0.05) and down regulated X-linked inhibitor of apoptosis protein. Apoptosis was blunted by Caspase-9 but not Caspase-8 inhibition. Uric acid induced changes in the mitochondrial membrane, elevations in reactive oxygen species and a pronounced up-regulation of NOX 4 mRNA and protein (p<0.05). In addition, both reactive oxygen species production and apoptosis was prevented by the NADPH oxidase inhibitor DPI as well as by Nox 4 knockdown. URAT 1 transport inhibition by probenecid and losartan and its knock down by specific siRNA, blunted apoptosis, suggesting a URAT 1 dependent cell death. In summary, our data show that uric acid increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signalling and URAT 1 transport. These results might explain the chronic tubulointerstitial damage observed in hyperuricaemic states and suggest that uric acid transport in tubular cells is necessary for urate-induced effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.